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Metallothionein Treatment Attenuates Microglial Activation and Expression of Neurotoxic Quinolinic Acid Following Traumatic Brain Injury
journal contribution
posted on 2023-05-17, 01:07 authored by Chung, RS, Jacqueline LeungJacqueline Leung, Butler, CW, Chen, Y, Eaton, ED, Pankhurst, MW, Adrian WestAdrian West, Guillemin, GJThe kynurenine pathway has been implicated as a major component of the neuroinflammatory response to brain injury and neurodegeneration. We found that the neurotoxic kynurenine pathway intermediate quinolinic acid (QUIN) is rapidly expressed, within 24 h, by reactive microglia following traumatic injury to the rodent neocortex. Furthermore, administration of the astrocytic protein metallothionein attenuated this neuroinflammatory response by reducing microglial activation (by approximately 30%) and QUIN expression. The suppressive effect of MT was confirmed upon cultured cortical microglia, with 1 lg/ml MT almost completely blocking interferon– gamma induced activation of microglia and QUIN expression. These results demonstrate the neuroimmunomodulatory properties of MT, which may have therapeutic applications for the treatment of traumatic brain injury.
History
Publication title
Neurotoxicity Research: An International Journal on Processes and Mechanisms in Neurodegeneration, Apoptosis, Neuroprotection and RegenerationVolume
15Issue
4Pagination
381-389ISSN
1029-8428Department/School
Menzies Institute for Medical ResearchPublisher
F P Graham Publishing CoPlace of publication
Po Box 370, Mountain Home, USA, Tn, 37684Repository Status
- Restricted